Abdominal Aortic Aneurysms (AAA) are a major cause of morbidity and mortality today, mostly affecting Caucasian men over the age of 60. AAA is a permanent dilation of the abdominal aorta that exceeds the normal aortic diameter by more than 50%. Rupture and blood clots are the life threatening risks associated with AAA. The current therapy for AAA is surgery, which is performed when the risk of rupture outweighs the risk of surgical intervention. Etiologically, AAA is characterized by a progressive degeneration of the three layers of the aortic wall. Normally, these layers secrete structural proteins, such as collagen and elastin, into the extracellular matrix (ECM) for crosslinking and vessel integrity. Matrix degeneration of the aortic wall is the hallmark of AAA. Currently, the only known and under investigated protein that stabilizes the aortic wall is a family of Lysyl Oxidase (LOX) enzymes that crosslink collagen and elastin in the ECM. LOX has not been previously implicated in AAA pathogenesis. In an unexpected observation, our lab in vivo model for atherosclerosis, an ApoE -/- mouse on a high fat diet (HF) infused with Angiotensin II (Ang II) developed AAA. Microarray analysis from our lab on these mice prior to AAA formation shows upregulated LOX expression as compared to control mice. Follow up infusion of B-APN, an irreversible inhibitor of LOX, caused AAA in 100% of the mice, supporting a role for LOX in AAA pathogenesis. Five different LOX enzymes exist in both humans and mice: Lysyl Oxidase (LOX) and the Lysyl Oxidase Like proteins (LOXL) - 1, -2, -3 and -4. Our microarray data did not reveal which LOX/LOXL family members were upregulated in AAA mice. Therefore our hypothesis is that Ang II upregulates LOX/LOXL family member expression and activity. Our proposed mechanism of action in regard to AAA is that LOX/LOXL family members work counter regulatory to matrix degradation to stabilize AAA and prevent rupture. Ang II increases LOX/LOXL activity, providing mechanical strength to the aortic wall. Previous immunohistochemical staining shows abundant LOX/LOXL family member expression in the medial layer of the aortic wall in AAA mice. Therefore smooth muscle cells will be the focus of our LOX/LOXL characterization. The proposed aims will address our hypothesis using an in vitro cell culture system, qRT-PCR, activity assays and western analysis to test 1.) LOX/LOXL family member expression in smooth muscle cells, 2.) Ang II regulation of LOX/LOXL family members, 3.) individual family member contribution to crosslinking activity and 4.) the functional significance of ROS byproducts. Understanding the pathogenesis of AAA is necessary to develop therapeutic intervention to stabilize AAA and prevent rupture, as an alternative to surgical intervention.